Target Set Research Articles

A model of human neural networks reveals NPTX2 pathology in ALS and FTLD

Human cellular models of neurodegeneration require reproducibility and longevity, which is necessary for simulating age-dependent diseases. Such systems are particularly needed for TDP-43 proteinopathies1, which involve human-specific mechanisms2–5 that cannot be directly studied in animal models. Here, to explore the emergence and consequences of TDP-43 pathologies, we generated induced pluripotent stem cell-derived, colony morphology neural stem cells (iCoMoNSCs) via manual selection of neural precursors6. Single-cell transcriptomics and comparison to independent neural stem cells7 showed that iCoMoNSCs are uniquely homogenous and self-renewing. Differentiated iCoMoNSCs formed a self-organized multicellular system consisting of synaptically connected and electrophysiologically active neurons, which matured into long-lived functional networks (which we designate iNets). Neuronal and glial maturation in iNets was similar to that of cortical organoids8. Overexpression of wild-type TDP-43 in a minority of neurons within iNets led to progressive fragmentation and aggregation of the protein, resulting in a partial loss of function and neurotoxicity. Single-cell transcriptomics revealed a novel set of misregulated RNA targets in TDP-43-overexpressing neurons and in patients with TDP-43 proteinopathies exhibiting a loss of nuclear TDP-43. The strongest misregulated target encoded the synaptic protein NPTX2, the levels of which are controlled by TDP-43 binding on its 3′ untranslated region. When NPTX2 was overexpressed in iNets, it exhibited neurotoxicity, whereas correcting NPTX2 misregulation partially rescued neurons from TDP-43-induced neurodegeneration. Notably, NPTX2 was consistently misaccumulated in neurons from patients with amyotrophic lateral sclerosis and frontotemporal lobar degeneration with TDP-43 pathology. Our work directly links TDP-43 misregulation and NPTX2 accumulation, thereby revealing a TDP-43-dependent pathway of neurotoxicity.

A67 REDUCING INAPPROPRIATE GAMMA-GLUTAMYL TRANSFERASE TESTING FOR INPATIENTS: A QUALITY IMPROVEMENT INITIATIVE IN LAB WASTE REDUCTION APPLYING THE MODEL FOR CONTINUOUS IMPROVEMENT

Abstract Background Review of the literature identifies a rising trend in laboratory testing, with over 30% of tests estimated to be inappropriately repeated. Laboratory overutilization increases healthcare costs, and can lead to overdiagnosis, overtreatment and negative health outcomes. Indications for repeat Gamma Glutamyl Transferase (GGT) testing in adults are limited, particularly repeat testing within the same admission. Aims Our aim was to reduce the inappropriate ordering of repeat GGT testing by 25% for all inpatients at the London Health Sciences Centre (LHSC) over a one-year study period. Methods An interprofessional team was created to help engage relevant stakeholders, collect baseline data and reassess the indications for GGT testing. A combination of root cause analysis tools, specifically the Ishikawa diagram and Pareto chart, were employed to identify potential factors contributing to the overutilization of GGT testing. After prioritizing potential solutions, intervention bundles were developed, and Plan-Do-Study-Act (PDSA) cycles were created to target correctable factors. In PDSA cycle #1, the process started by eliminating GGT as a laboratory testing option in the three most commonly used admission order care sets. Considering the hierarchy of intervention effectiveness, PDSA cycle #2 involved implementing a computerized Clinical Decision Support (CDS) system to restrict the reordering of GGT tests within 72 hours of the same admission. Results Baseline data showed that in 2022, a total of 62,542 GGT tests were ordered, with an average of approximately 5,200 GGT tests ordered per month. Of these, 16.4% were ordered through the top 3 most prevalent admission order care sets, and around 25% of all GGT tests were repeats within 72 hours of admission. Referring to Figure 1, PDSA cycle #1 yielded no significant reduction in GGT testing. PDSA cycle #2 successfully reduced the proportion of repeat GGT tests ordered by 12% within two months of implementation, leading to an estimated annualized cost savings of approximately $37,440. Conclusions Our results establish the effectiveness of CDS systems in reducing laboratory testing overutilization, suggesting their superiority to individual care set targeting interventions, and emphasize the potential for cost-effective CDS development in contemporary healthcare. Funding Agencies None

What is the basis of ensemble subset selection?

The visual system can rapidly calculate the ensemble statistics of a set of objects; for example, people can easily estimate an average size of apples on a tree. To accomplish this, it is not always useful to summarize all the visual information. If there are various types of objects, the visual system should select a relevant subset: only apples, not leaves and branches. Here, we ask what kind of visual information makes a "good" ensemble that can be selectively attended to provide an accurate summary estimate. We tested three candidate representations: basic features, preattentive object files, and full-fledged bound objects. In four experiments, we presented a target and several distractors' sets of differently colored objects. We found that conditions where a target ensemble had at least one unique color (basic feature) provided ensemble averaging performance comparable to the baseline displays without distractors. When the target subset was defined as a conjunction of two colors or color-shape partly shared with distractors (so that they could be differentiated only as preattentive object files), subset averaging was also possible but less accurate than in the baseline and feature conditions. Finally, performance was very poor when the target subset was defined by an exact feature relationship, such as in the spatial conjunction of two colors (spatially bound object). Overall, these results suggest that distinguishable features and, to a lesser degree, preattentive object files can serve as the representational basis of ensemble selection, while bound objects cannot.

Stability of grain zinc concentrations across lowland rice environments favors zinc biofortification breeding.

One-third of the human population consumes insufficient zinc (Zn) to sustain a healthy life. Zn deficiency can be relieved by increasing the Zn concentration ([Zn]) in staple food crops through biofortification breeding. Rice is a poor source of Zn, and in countries predominantly relying on rice without sufficient dietary diversification, such as Madagascar, Zn biofortification is a priority. Multi-environmental trials were performed in Madagascar over two years, 2019 and 2020, to screen a total of 28 genotypes including local and imported germplasm. The trials were conducted in the highlands of Ankazomiriotra, Anjiro, and Behenji and in Morovoay, a location representative of the coastal ecosystem. Contributions of genotype (G), environment (E), and G by E interactions (GEIs) were investigated. The grain [Zn] of local Malagasy rice varieties was similar to the internationally established grain [Zn] baseline of 18-20 μg/g for brown rice. While several imported breeding lines reached 50% of our breeding target set at +12 μg/g, only few met farmers' appreciation criteria. Levels of grain [Zn] were stable across E. The G effects accounted for a main fraction of the variation, 76% to 83% of the variation for year 1 and year 2 trials, respectively, while GEI effects were comparatively small, contributing 23% to 9%. This contrasted with dominant E and GEI effects for grain yield. Our results indicate that local varieties tested contained insufficient Zn to alleviate Zn malnutrition, and developing new Zn-biofortified varieties should therefore be a priority. GGE analysis did not distinguish mega-environments for grain [Zn], whereas at least three mega-environments existed for grain yield, differentiated by the presence of limiting environmental conditions and responsiveness to improved soil fertility. Our main conclusion reveals that grain [Zn] seems to be under strong genetic control in the agro-climatic conditions of Madagascar. We could identify several interesting genotypes as potential donors for the breeding program, among those BF156, with a relatively stable grain [Zn] (AMMI stability value (ASV) = 0.89) reaching our target (>26 μg/g). While selection for grain yield, general adaptation, and farmers' appreciation would have to rely on multi-environment testing, selection for grain [Zn] could be centralized in earlier generations.

Analysis of the Ratio of Growth, Effectiveness and Budget Efficiency at the Ministry of Religious Affairs of the Republic of Indonesia in 2017 – 2022

A budget is a written plan regarding the activities of an organization which is expressed quantitatively for a certain period or period and is generally expressed in units of money. The Ministry of Religion of the Republic of Indonesia is one of the ministries that has authority over the State revenue and expenditure budget. The Ministry of Religion is ranked 2nd with the largest APBN ceiling after the Police of the Republic of Indonesia. The ratios for assessing financial performance in the Ministry of Religion used in this research include: Growth Ratio, Effectiveness and Efficiency Ratio. This research aims to analyze the level of Growth, Effectiveness and Efficiency Ratios during the 2017-2022 period to see the financial performance of the Ministry of Religion of the Republic of Indonesia. In writing this journal, a quantitative descriptive analysis method was used. The results of this research show that the financial performance of the Ministry of Religion using the Growth Ratio or the Ministry of Religion's budget growth ratio is around 4.39% every year. The Ministry of Religion's budget effectiveness ratio is relatively high at an average level of 112%, which means that budget realization is able to exceed the set targets. The highest achievement of 121% was recorded in 2017. The Ministry of Religion's budget efficiency ratio for 2017-2022 is at an average of 0.97%, which is very efficient considering the nature of the public sector budget, the smaller the efficiency ratio, the better the government's performance.

Mediating Role of Collaboration on Transformational Leadership and Performance Contracts in Road Agencies in Kenya.

Purpose: Type of leadership that can be considered effective, in the current set of environments would demand collaboration, listening skills, influence, and flexible adaptation to the existing environment in contrary to command and control systems in organizations. This study investigated the mediating role of collaboration to the relationship between transformational leadership and performance contracting in road agencies in Kenya. Operationalization of variables included transformational leadership as independent variable, performance contracting as the dependent variable and collaboration as the mediating variable. This study was guided by theories of transformational leadership and public value.
 Methodology: The study adopted mixed methods approach where data was collected through questionnaires and structured interviews and target population for the research was all staff members in top management and officers in job group 5 (five) and above for three road agencies in Kenya. The road agencies included Kenya National Highway Authority (KeNHA), Kenya Urban Roads Authority (KURA) and Kenya Rural Roads Authority (KeRRA). The study utilized descriptive and inferential statistics used data analysis where regression was computed to determine correlations between independent, mediating and dependent variables.
 Findings: From the study findings and results, the relationship between transformational leadership and performance contracting in road agencies in Kenya was noted to be partially mediated by collaboration as p value was (p< 0.05). Collaboration was therefore noted as a very important component in an organization as employees are able to achieve their performance targets with ease as different sections and individuals support each in the process of performance contracting in road agencies in Kenya. This study recommends to policy makers in road agencies in Kenya to create a conducive environment of collaboration and teamwork as the same would enhance both individual and collective performance which ultimately influence levels of achievement of set targets in performance contracts in these organization.
 Unique contributor to theory, policy and practice: This study recommends further areas of research in general or overall performance of road agencies in Kenya and teamwork building processes, role of leadership in teamwork and in achieving individual and organizational performance.

Management Practices and Implementation Challenges in District Education Directorates in Ghana

Background: Subnational actors and organizations are crucial mediators of policy implementation due to their proximity to schools. However, in low- and middle-income country contexts, little is known about their management practices and factors that shape the adoption of these practices to improve education delivery. Purpose: We explore the management context of five District Education Directorates in Ghana, and the factors that enable or constrain them to plan and implement policy. Participants: Forty-three interviews and focus groups with regional and district education officials, district political actors, and basic education school headteachers and teachers. Research Design: A qualitative study of semistructured interviews, focus groups, and education policy and planning documents. Analysis: To understand how policy implementation happens within complex, multitiered bureaucracies, our theoretical framework uses four management functions described in Williams et al. (2021) to explore two different paradigms of how to change public bureaucracies: target setting and prioritization; measurement and monitoring; accountability and incentives; and problem-solving. We coded and analyzed our data based on this framework and developed district-wide narrative memos to synthesize the findings. Findings: We identify three areas of (mis)alignment in management practices: across bureaucratic levels and among actors; around clear and consistent priorities for learning; in expected actions and availability of resources. These (mis)alignments can constrain or be leveraged by districts to improve education delivery in Ghana. Implications: We argue for better prioritization of goals toward learning and the efficient allocation of funds for management practices typical of effective organizations.

Analisis Efektivitas dan Kontribusi Penerimaan Pajak Bumi dan Bangunan (PBB) terhadap Pendapatan Asli Daerah di Kota Medan: Study Kasus Kantor Dispenda Medan

This study aims to : (1) Analyze Land and Building Tax (PBB) revenues in accordance with the targets set during 2017 to 2021 ; (2) Determine the contribution of Land and Building Tax (PBB) revenues to Regional Original Income (PAD) in the Medan City government from 2017 to 2021 ; (3) Analyze the factors that led to a decrease in the number of Tax Returns Payable (SPPT) in paying Bunt and Building Tax (PBB) in 2017 to with 2021. In this study the authors took a descriptive approach, the data source used primary data. The data analysis technique used in this study used the effevtiveness ratio and contribution formula. The result of this study advanced that (1) Realization of Land and Building Tax (PBB) revenues in general reched the target set with the average revenue effectiveness categorized as quite effective (2) The contribution of Land and Building Tax (PBB) to Regional Original Income (PAD) has agretes value compared to other regional taxes with an average contribution categorized as moderate (3) Factors that influence the reduction of Tax Returns Payable (SPPT) in paying taxes caused by internal factors and external factors

ALR_Sim_tracks — Trajectory Simulator Software to Assist the Search for Favourable Trajectories for the Exploration of the Triple Asteroid 2001-SN263 From the Laser Altimeter Point of View

This paper presents a simulator tool, named _ALR_Sim_tracks_, dedicated to the preliminary analysis of trajectories planned for a space mission to explore the surface of celestial bodies using optical sensors, such as a laser altimeter. The software offers a prediction of the coverage results obtainable in a simulated exploration campaign carried out along a selected/simulated trajectory, for the set of target and instrument parameters used (in qualitative and quantitative terms, including 2D/3D visualizations). The software was created to perform an analysis that would allow the identification of favourable trajectories for conducting the intended exploration of the triple asteroid 2001-SN263 during Brazil's first deep space mission (ASTER mission) from the point of view of the Laser Altimeter being designed to fly in this mission, which was named ALR. Because there are few tools described and available for this type of analysis in the literature, and these are generally complex, proprietary and of restricted use, this work aims to help broaden the understanding of the process involved and the access to this type of tool. The paper contains the description of the _ALR_Sim_tracks_ software and everything involved in its operation. The illustrative examples presented in this text involve the exploration of an asteroid from the point of view of a laser altimeter, because this was the initial motivation for creating the simulator. However, other optical instruments with similar operation, used to explore other types of targets (e.g. planets or moons), are also considered when suitable modelling is available.

Pengembangan Kurikulum Berbasis STEAM (Science, Technology, Engineering, Arts, and Mathematics) untuk Meningkatkan Kreativitas dan Kemampuan Berfikir Kritis

In learning process activities, the curriculum is really needed as a guide to setting targets and making the teaching and learning process easier. The curriculum will be easy to implement through several approaches, one of which is a STEAM (Science, Technology, Engineering, Arts, and Mathematics) based approach. This research aims to analyze the development of a STEAM-based curriculum to increase creativity and critical thinking skills. The research method used is the literature review method. Sources of information can be books, journals, ebooks, or other scientific articles. The results of this research are that the STEAM approach is able to increase students' creativity and critical thinking power. The STEAM learning model is a learning innovation that can be applied at all levels of education. It is designed to equip students with various skills to face various changes in the world, including the challenges of advances in science and technology in the field of education.

A Bilevel DEA Model for Efficiency Evaluation and Target Setting with Stochastic Conditions

The effective allocation of limited resources and the establishment of targeted goals play a pivotal role in enhancing the overall efficiency of large enterprises and organizations. To achieve optimal organizational efficiency, managers seek dynamic strategies that adapt to the constraints of limited and uncertain historical data. This paper introduces an evaluation of organizational efficiency through a stochastic framework, employing a bilevel data envelopment analysis (DEA) approach. This decision-making process is centralized within a decision-making unit (DMU) overseeing subordinate decision-making units (subDMUs). Discrete scenarios, each associated with a realization probability, define the uncertain parameters in the bilevel DEA-based model. This stochastic approach allows for recourse actions upon scenario realization leading to an enhanced overall organizational strategy. Decision-makers acting within uncertain and dynamic environments can benefit from this research since it allows the investigation of efficiency assessment under alternative scenarios in the presence of volatility and risk. The potential impact of applying this methodology varies depending on the specific domain. Although, the context of this paper focuses on banking, in general, enhancing resource allocation and target setting under stochasticity, contributes to advancing sustainability across all its three dimensions (economic, environmental, social). As mentioned earlier, the practical application of our approach is demonstrated via a case study in the banking sector.

Chemical constituents from Microstachys chamaelea (Euphorbiaceae) with cytotoxic and antioxidant properties

Phytochemical investigation of Microstachys chamaelea led to the isolation and identification of fourteen known compounds after analysis of spectroscopic data. They consist of eight flavonoids (1–8), two benzoic acid derivatives (9–10), one brevifolin carboxylic acid derivative (11), one geraniinic acid derivative (12), shikimic acid (13), and β-daucosterol (14). Remarkably, it is the second isolation of compound 12 from a natural source. Several isolates were evaluated against ten cancer cell lines and on a set of targets involved in oxidative stress, as no such assays were undertaken in previous works. Compound 7 showed moderate to strong cytotoxicity against eight cell lines (IC50 values of 6.0–39.0 µM), while compounds 2, 8, and 11 showed weak to moderate cytotoxicity. Compounds 1–3, 5, and 11–12 showed moderate to strong DPPH and XXO inhibitory activities (IC50 values of 13.1–16.5 and 6.0–69.0 µM, respectively).

Digital interventions targeting excessive substance use and substance use disorders: a comprehensive and systematic scoping review and bibliometric analysis.

Addictive substances are prevalent world-wide, and their use presents a substantial and persistent public health problem. A wide range of digital interventions to decrease use and negative consequences thereof have been explored, differing in approach, theoretical grounding, use of specific technologies, and more. The current study was designed to comprehensively map the recent (2015-2022) extant literature in a systematic manner, and to identify neglected and emerging knowledge gaps. Four major databases (Medline, Web of Science Core Collection, and PsychInfo) were searched using database-specific search strategies, combining terms related to clinical presentation (alcohol, tobacco or other drug use), technology and aim. After deduplication, the remaining n=13,917 unique studies published were manually screened in two stages, leaving a final n=3,056 studies, the abstracts of which were subjected to a tailored coding scheme. Findings revealed an accelerating rate of publications in this field, with randomized trials being the most common study type. Several meta-analyses on the topic have now been published, revealing promising and robust effects. Digital interventions are being offered on numerous levels, from targeted prevention to specialized clinics. Detailed coding was at times made difficult by inconsistent use of specific terms, which has important implications for future meta-analyses. Moreover, we identify several gaps in the extant literature - few health economic assessments, unclear descriptions of interventions, weak meta-analytic support for some type of interventions, and limited research on many target groups, settings and new interventions like video calls, chatbots and artificial intelligence - that we argue are important to address in future research.

Optimal Control of Probability on a Target Set for Continuous-Time Markov Chains

In this paper, a stochastic optimal control problem is considered for a continuous-time Markov chain taking values in a denumerable state space over a fixed finite horizon. The optimality criterion is the probability that the process remains in a target set before and at a certain time. The optimal value is a superadditive capacity of target sets. Under some minor assumptions for the controlled Markov process, we establish the dynamic programming principle, based on which we prove that the value function is a classical solution of the Hamilton-Jacobi-Bellman equation on a discrete lattice space. We then prove that there exists an optimal deterministic Markov control under the compactness assumption of control domain. We further prove that the value function is the unique solution of the HJB equation. We also consider the case starting from the outside of target set and give the corresponding results. Finally, we apply our results to two examples.

Policy and hope: The millennium development goals

AbstractThe Millennium Development Goals (MDGs) were a set of measurable goals and targets agreed to by all United Nations (UN) member countries in 2001 or thereafter to achieve substantial socio‐economic improvement for all developing countries by 2015. The MDGs were defined by some as an ‘international super‐norm’ that made the eradication of extreme poverty a global policy and responsibility. In this article, we examine the broader historical and discursive context that facilitated this institutional emergence and draw on Rorty and Braithwaite to suggest that the MDGs can be considered an ‘institution of hope.’ The paper contextualises the political economy of despair that prevailed in the 1990s before outlining Rorty's critique of neo‐liberalism and post‐developmentalism and explaining the political value of hope as a collective motivating emotion. The paper then examines critiques of the MDGs before concluding that the MDGs performed a valuable function in reinvigorating global concern over poverty eradication, even if, in retrospect, the MDGs themselves remained only what Rorty referred to as a ‘plausible narrative of progress.’

Advances in machine learning with chemical language models in molecular property and reaction outcome predictions.

Molecular properties and reactions form the foundation of chemical space. Over the years, innumerable molecules have been synthesized, a smaller fraction of them found immediate applications, while a larger proportion served as a testimony to creative and empirical nature of the domain of chemical science. With increasing emphasis on sustainable practices, it is desirable that a target set of molecules are synthesized preferably through a fewer empirical attempts instead of a larger library, to realize an active candidate. In this front, predictive endeavors using machine learning (ML) models built on available data acquire high timely significance. Prediction of molecular property and reaction outcome remain one of the burgeoning applications of ML in chemical science. Among several methods of encoding molecular samples for ML models, the ones that employ language like representations are gaining steady popularity. Such representations would additionally help adopt well-developed natural language processing (NLP) models for chemical applications. Given this advantageous background, herein we describe several successful chemical applications of NLP focusing on molecular property and reaction outcome predictions. From relatively simpler recurrent neural networks (RNNs) to complex models like transformers, different network architecture have been leveraged for tasks such as de novo drug design, catalyst generation, forward and retro-synthesis predictions. The chemical language model (CLM) provides promising avenues toward a broad range of applications in a time and cost-effective manner. While we showcase an optimistic outlook of CLMs, attention is also placed on the persisting challenges in reaction domain, which would optimistically be addressed by advanced algorithms tailored to chemical language and with increased availability of high-quality datasets.

Dissemination and implementation of an evidence-based voluntary medical male circumcision program: The Spear & Shield program.

Despite compelling evidence linking voluntary medical male circumcision (VMMC) with 60-70% HIV risk reduction in sub-Saharan Africa, Zambian men have been especially reluctant to undergo VMMC. The Government of Zambia set targets for VMMC uptake and promoted community-level interventions. Spear & Shield (S&S) is an innovative, evidence-based, service program promoting VMMC uptake while ensuring both VMMC supply and demand. This study assessed the large-scale provincial rollout of the program (S&S2) utilizing the RE-AIM model for translating interventions into the community. The S&S2 study was conducted between November 2015 and December 2020, and sequentially rolled out over four Zambian provinces in 96 clinics; 24 observation clinics received VMMC training only. Local clinic healthcare workers were trained to conduct the VMMC procedure and HIV counselors were trained to lead S&S group sessions. Using the RE-AIM model, primary outcomes were: Reach, the number, proportion, and representativeness of S&S attendees; Effectiveness, the impact of S&S2 on VMMC uptake; Adoption, the number, proportion, and representativeness of clinics implementing S&S2; Implementation, fidelity to the S&S intervention manual; and Maintenance, the extent to which S&S2 became an element of standard care within community clinics. Initially, n = 109 clinics were recruited; 96 were sustained and randomized for activation (Adoption). A total of 45,630 clinic patients (n = 23,236 men and n = 22,394 women) volunteered to attend the S&S sessions (Reach). The S&S2 program ran over 2,866 clinic-months (Implementation). Although the study did not target individual-level VMMCs, ~58,301 additional VMMCs were conducted at the clinic level (Effectiveness). Fidelity to the S&S intervention by group leaders ranged from 42%-95%. Sustainability of the program was operationalized as the number of CHCs initially activated that sustained the program. Intervention delivery ended, however, when study funding ceased (Maintenance). The S&S2 program successfully utilized the RE-AIM model to achieve study goals for implementation and dissemination in four Zambian provinces. Innovative VMMC programs such as S&S2 can improve the uptake of VMMC, one of the most effective strategies in the HIV prevention arsenal.

A novel model for merger analysis and target setting: A CSW-Inverse DEA approach

The inverse data envelopment analysis (DEA) is an advanced complementary method for efficiency analysis using the classical DEA approach. One of the inverse DEA (InvDEA) method applications is the mergers and acquisitions problem. It can be used for analyzing any under evaluation mergers and acquisitions. The current article is the first attempt to propose a novel inverse structure for the DEA model using the multiplier forms. This eventuates the possibility of incorporating decision maker preferences within the merger analysis.Moreover, compared with the existing models in the literature, the proposed novel models are capable of analyzing multiple merger scenarios simultaneously in a single method based on the common set of weights (CSW) rather than a series of models for studying multiple scenarios of mergers and acquisitions. Practically, this property enables decision-makers to consider and analyze multiple mergers and find possible potentials at the same time. The applicability of the proposed model is investigated by using a real-world dataset in banking.

Extended Cleavage Specificity of two Hematopoietic Serine Proteases from a Ray-Finned Fish, the Spotted Gar (Lepisosteus oculatus).

The extended cleavage specificities of two hematopoietic serine proteases originating from the ray-finned fish, the spotted gar (Lepisosteus oculatus), have been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated using a panel of recombinant substrates. For one of the enzymes, the gar granzyme G, a strict preference for the aromatic amino acid Tyr was observed at the cleavable P1 position. Using a set of recombinant substrates showed that the gar granzyme G had a high selectivity for Tyr but a lower activity for cleaving after Phe but not after Trp. Instead, the second enzyme, gar DDN1, showed a high preference for Leu in the P1 position of substrates. This latter enzyme also showed a high preference for Pro in the P2 position and Arg in both P4 and P5 positions. The selectivity for the two Arg residues in positions P4 and P5 suggests a highly specific substrate selectivity of this enzyme. The screening of the gar proteome with the consensus sequences obtained by substrate phage display for these two proteases resulted in a very diverse set of potential targets. Due to this diversity, a clear candidate for a specific immune function of these two enzymes cannot yet be identified. Antisera developed against the recombinant gar enzymes were used to study their tissue distribution. Tissue sections from juvenile fish showed the expression of both proteases in cells in Peyer's patch-like structures in the intestinal region, indicating they may be expressed in T or NK cells. However, due to the lack of antibodies to specific surface markers in the gar, it has not been possible to specify the exact cellular origin. A marked difference in abundance was observed for the two proteases where gar DDN1 was expressed at higher levels than gar granzyme G. However, both appear to be expressed in the same or similar cells, having a lymphocyte-like appearance.

Spatially coordinated conservation auctions: A framed field experiment focusing on farmland wildlife conservation in China

AbstractHow best to incentivize land managers to achieve conservation goals in an economically and ecologically effective manner is a key policy question that has gained increased relevance from the setting of ambitious new global targets for biodiversity conservation. Conservation (reverse) auctions are a policy tool for improving the environmental performance of agriculture, which has become well‐established in the academic literature and in policy making in the US and Australia. However, little is known about the likely response of farmers to incentives within such an auction to (1) increase spatial connectivity and (2) encourage collective participation. This paper presents the first framed field experiment with farmers as participants that examines the effects of two features of conservation policy design: joint (collective) participation by farmers and the incentivization of spatial connectivity. The experiment employs farmers in China, a country making increasing use of payments for ecosystem services to achieve a range of environmental objectives. We investigate whether auction performance—both economic and ecological—can be improved by the introduction of agglomeration bonus and joint bidding bonus mechanisms. Our empirical results suggest that, compared to a baseline spatially coordinated conservation auction, the performance of an auction with an agglomeration bonus, a joint bidding bonus, or both, is inferior on two key metrics—the environmental benefits generated and cost effectiveness realized.